(1) The epidermal growth factor receptor (EGFR) and its truncated counterpart efficiently couples with mitogenic signalling pathways when transfected into interleukin-3 (IL-3)-dependent 32D hematopoietic cells. When expression vectors for erbB-2, which is related to EGFR, or its truncated counterpart, were introduced into 32D cells, neither induced proliferation. This was despite overexpression and constitutive tyrosine kinase activity of their products at levels associated with potent transformation of fibroblasts. Thus, EGFR and erbB-2 couple with distinct mitogenic signalling pathways . ( 2) A human CSF-1 receptor vector was transfected into the IL-3-dependent 32D cells. Human CSF-1/c-fms triggered proliferation in association with synchronous monocyte differentiation of the 32D-c-fm cells which was reversible upon removal of CSF-1. Thus, CSF-1 was not sufficient to induce irrevocable differentiation commitment. Human CSF-1 was also shown to be a potent chemoattractant for 32D-c-fms cells, suggesting that it may serve to recruit monocytes from circulation to tissue sites of inflammation or injury. Expression of mutated c-fm in 32D cells abrogated their IL-3 requirement and induce tumorigenicity. These cells also displayed a mature monocyte phenotype, implying that differentiation did not interfere with progression to the malignant state. (3) The oncogenic potential of the erbB-2 gene in human mammary epithelial cells was analyzed. Overexpression of normal erbB-2 in the normal 184B5 mammary epithelial line allowed for low-level growth in soft agar and rare tumor formation in athymic mice. However, overexpression of genetically altered erbB-2 led to high efficiency colony formation and tumorigenicity. These results strengthen the hypothesis that erbB-2 plays an important role in human breast carcinoma.